Work

Fibrogenesis Biomarkers and Clinical Disease Progression in ADPKD

Year: 2026

Type: article

Abstract: Introduction Fibrogenesis contributes to disease progression in patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD). In this exploratory study, we evaluated the association of protease-generated circulating and urinary collagen fragments (C3M, PRO-C3, and PRO-C6), reflecting fibrogenesis and fibrolysis, with clinical outcomes in ADPKD. Methods We included 302 patients from the DIPAK-1 trial (lanreotide vs. standard treatment), with a mean baseline age of 48.9 ± 7.3 years and eGFR of 51.3 ± 11.5 ml/min/1.73m 2 . Kidney endpoints were eGFR slope, rapid disease progression (eGFR loss ≥ 3 ml/min/1.73m 2 /year), and a composite kidney endpoint (30% eGFR loss or initiation of kidney replacement therapy). Net benefit analysis was performed to assess clinical utility. Results During 2.4 ± 0.4 years of follow-up, mean eGFR slope was -4.02 ± 3.64 ml/min/1.73m 2 /year, 190 patients (62.9%) had rapid disease progression, and 87 (28.8%) reached the composite endpoint. After adjustment for sex, baseline age, baseline eGFR, Mayo imaging class, PKD pathogenic variant and treatment group, uPRO-C3/Cr and uPRO-C6/Cr were independently associated with eGFR slope, rapid disease progression, and the composite endpoint. uPRO-C3/Cr was also associated with HtTKV growth rate. Adding uPRO-C3/Cr or uPRO-C6/Cr improved prediction of rapid disease progression, increasing AUC from 0.78 (95% CI: 0.73, 0.86) to 0.79 (95% CI: 0.73, 0.86) and 0.80 (95% CI: 0.73, 0.86), respectively. Decision curve analysis did not demonstrate a meaningful net benefit. Conclusion These findings demonstrate that uPRO-C3/Cr and uPRO-C6/Cr were independently associated with kidney outcomes in ADPKD, providing clinical evidence that ECM remodeling is associated with ADPKD disease progression.

Source: Kidney International Reports

DOI: 10.1016/j.ekir.2026.107102